PROJECT SUMMARY Central nervous system (CNS) diseases, including Alzheimer's disease (AD), represent a daunting challenge for the development of novel drugs. The successful development and commercialization of next- generation, low-cost, high-performance technology for modeling both disease biology and the effects of investigational drugs on neurons, would help improve the development process for new therapies?thereby reducing national healthcare costs and improving patient outcomes throughout the nation. The ability to prepare disease models from stable, reproducible neuronal cultures in vitro would allow screening and prioritization of further testing in a rapid and cost-effective manner. Ideally, this system could be expanded to incorporate disease models that would mimic in vivo as well as clinical findings. Therefore, the overall goal of this multi-phase SBIR project is to develop, validate, and commercialize an in vitro high throughput, high content phenotypic neuronal assay for AD to allow Phenovista's proprietary neuronal culture screening system, a next-generation in vitro system for ranking the relative efficacy and toxicity of CNS therapies, to be incorporated as a part of the regulatory framework for therapeutic commercialization. 1